The major objectives are to determine the mechanisms by which the angiotensins and kinins are formed, exert their actions and are inactivated. Formation of angiotensin II will be studied using synthetic angiotensin I labelled specifically with C14. Formation and entry of kinins into the circulation will be examined using hybrid isotope-dilution-radioimmunoassay techniques. Similar techniques will be developed for studying the formation of angiotensin I. The actions of kinins and angiotensins will be studied first by examining the relevance of solution structures to biologic effects. The parent peptide hormones and their analogs and homologs will be prepared by solid-phase synthesis and characterized in terms of circular dichoroism spectra and biological actions. Degradation of vasoactive polypeptides will be studied by perfusin C14 or H3-labelled peptide through major vascular beds. Because of its extensive capillary network and its strategic position within the circulation, first studies will focus on metabolism of peptide hormones within the lungs. Possible cellular sites of the lung metabolic enzymes will be examined by electron microscopy and biochemical characterization of enzymic activities of subcellular fractions.